A variety of methods and compositions are known to administer pharmaceuticals and/or cosmetics. The controlled administration of bioactive substances, such as pharmaceuticals, has become an increasingly important mode of treatment for any diseases and disorders. Pharmaceutical manufactures have designed products to gradually release bioactive substances at a therapeutically useful rate and to spatially target the release, for example by use of a valving system, or physically as by slow diffusion. However, many of these techniques are invasive and/or cumbersome.
Iontophoresis is a technique used to enhance the penetration of topically applied drugs or other substances on skin and mucous membranes. Examples of such use include: Gangarosa et al, J. Pharm. Sci. (October 1979) 67(10):1439-1443 which describes the conductivity of a variety of drugs; Gangarosa et al, Ear. Nose & Throat (December 1982) 61:30-41 which describes a variety of drugs for the management of temporomandibular joint-myofascial pain dysfunction syndrome; Gangarosa et al., Proc. Soc. Exper. Bio. & Med. (1986) 181(3):476 which describes electrostatic repulsion of positively charged drugs, like pilocarpine or lidocaine, for pain relief in postherpetic neuralgia; Tyle, P., Pharm. Res. (1986) 3(6):318-326 which is a review of devices for iontophoresis drug delivery; Sloan et al. J. Am. Acad. Derm. (October 1986) 15(4,pt 1):671-684 which is a review of iontophoresis in dermatology; and Sloan et al, Drug Design & Delivery (1989) 4:1-12 which is a review of transdermal delivery of drugs by iontophoresis.
Iontophoresis is based on electrostatic repulsion i.e., positively charged drugs penetrate tissues more, if a positive electrode is placed on the site of application. Penetration of drugs having negative charge can be enhanced similarly with a negative electrode. Obviously the penetration of non-polar drugs cannot be infused by this type of drug delivery system. Iontophoresis has had limited utility for application of substances and has suffered from a number of disadvantages, including quantification control and the necessity to combine the active ingredient with a relatively large quantity of a carrier liquid to the area to be treated or tested.
Accordingly, there is still a need to overcome difficulties that are encountered in therapeutic or experimental administration where it is desirable to release discrete units of highly active agents, particularly in vivo, to non-invasively administer materials which are normally uncharged and to administer substances to unbroken skin which provides a proper rate of permeation without discomfort or risk of undesirable discomfort or reaction.